Purpose

To characterize ocular phenotypes in patients with CTNNB1, KIF11, or NDP variants.

Design

Retrospective case series.

Methods

Seventy-four patients from 59 unrelated families with CTNNB1, KIF11, and NDP variants were enrolled based on exome sequencing. The clinical data of ophthalmoscope, fundus photography, fluorescein angiography, and ocular ultrasound scan were evaluated.

Results

A total of 55 potential pathogenic variants were identified, including 26 in KIF11 (28 families), 23 in NDP (25 families), and 6 in CTNNB1 (6 families). In total, 74 patients from the 59 families carried the variants, in whom clinical data were available from 70 patients for the current analysis. Severe familial exudative vitreoretinopathy (FEVR), stages 4 and 5, was present in 72.9% (51/70) of patients. In addition, panretinal or sector chorioretinal degeneration along with FEVR is a specific feature associated with KIF11 variants, present in 93.8% (30/32) of patients. FEVR-like change was observed in almost all patients with rare hemizygous variants in NDP, patients with heterozygous truncation variants in CTNNB1, as well as patients with heterozygous truncation or damaging missense variants in KIF11.

Conclusions

Severe FEVR-like change with or without significant chorioretinopathy is a common feature in addition to neurodevelopmental disorders for variants in CTNNB1, KIF11, and NDP. In our cohort, the frequency of families with variants in KIF11 was comparable to that in TSPAN12, so as for NDP. Recognizing the characteristics of variants in the 3 genes and associated ocular phenotypes may enrich our understanding and potential management of this disease.

中文翻译：

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严重渗出性玻璃体视网膜病变是 CTNNB1、KIF11 和 NDP 变体的共同特征加上 KIF11 的部门变性

目的

表征具有CTNNB1、KIF11或NDP变体的患者的眼表型。

设计

回顾性案例系列。

方法

根据外显子组测序，招募了来自 59 个无关家庭的具有CTNNB1、KIF11和NDP变体的 74 名患者。评估检眼镜、眼底照相、荧光血管造影和眼部超声扫描的临床数据。

结果

共鉴定出55个潜在致病变异，其中KIF11 26个（28个家族），NDP 23个（25个家族），CTNNB1 6个（6个家族）。总共有来自 59 个家族的 74 名患者携带这些变异，其中 70 名患者的临床数据可用于当前分析。72.9% (51/70) 的患者存在严重的家族性渗出性玻璃体视网膜病变 (FEVR)，第 4 期和第 5 期。此外，全视网膜或部分脉络膜视网膜变性以及 FEVR 是与KIF11变体相关的特定特征，存在于 93.8% (30/32) 的患者中。在NDP中几乎所有具有罕见半合子变异的患者中都观察到 FEVR 样变化, CTNNB1中具有杂合截断变异的患者，以及KIF11中具有杂合截断或破坏性错义变异的患者。

结论

除了CTNNB1、KIF11和NDP变异的神经发育障碍外，伴有或不伴有明显脉络膜视网膜病变的严重 FEVR 样变化是常见特征。在我们的队列中， KIF11中具有变异的家族的频率与TSPAN12中的频率相当，对于NDP也是如此。认识到这 3 个基因的变异特征和相关的眼表型可能会丰富我们对这种疾病的理解和潜在的管理。